National Cancer Institute

at the National Institutes of Health

Annual Report to the Nation on the Status of Cancer, 1975–2009, Featuring the Burden and Trends in HPV-Associated Cancers and HPV Vaccination Coverage Levels: Questions and Answers

Posted: January
7, 2013

Key Points

Overall cancer death rates continued to decline among men (1.8% per year), women (1.4% per year), and children (1.8% per year), during 2000-2009. (Question 7)

During 2000-2009, overall cancer incidence rates decreased by 0.6% per year among men, were stable among women, and increased by 0.6% per year among children (Question 5)

Incidence rates of some HPV-associated cancers increased during 2000-2009, including oropharyngeal cancer among white men and women and anal cancer among white and black men and women. Rates of cervical cancer generally declined among almost all women. (Question 14)

In 2010, approximately 32% of girls aged 13-17 years had received the recommended three doses of the HPV vaccine in the United States, which is much lower than the coverage reported in neighboring countries and in many European nations. (Question 16)

1. What is the purpose of this report and who created it?This report provides a regular update of cancer incidence (new cases) and mortality (death) rates and trends in these rates in the United States. The American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), part of the National Institutes of Health, and the North American Association of Central Cancer Registries (NAACCR) have collaborated since 1998 to create the Annual Report to the Nation on the Status of Cancer. The special feature section of this year’s report highlights the burden and trends in human papillomavirus (HPV)-associated cancers as well as HPV vaccination coverage levels among adolescent girls.

2. What are the sources of the data?Cancer mortality information in the United States is based on causes of death reported by physicians on death certificates and filed by each state’s vital statistics offices. The mortality information is processed and consolidated in a national database by the CDC through the National Vital Statistics System, which covers the entire United States.

Information on newly diagnosed cancer cases occurring in the United States is based on data collected by registries in the CDC's National Program of Cancer Registries (NPCR) and NCI's Surveillance, Epidemiology, and End Results (SEER) Program. NAACCR evaluates data annually from registries in both programs and provides combined data for this analysis.

Long-term (1992-2009) overall incidence trends for all cancer sites combined and for the 15 most common cancers were based on SEER incidence data covering about 14 percent of the U.S. population. Data from combined NPCR and SEER population-based cancer registries were used to estimate cancer incidence rates and short-term (2000-2009) trends for each of five major racial and ethnic groups: white, black, Asian and Pacific Islander, American Indian/Alaska Native, and Hispanic. For the time period 2005-2009, 47 registries (covering 93 percent of the U.S. population) met NAACCR data quality criteria, and for the time period 2000-2009, 42 registries (covering 87 percent of the U.S. population) met these criteria.

3. Which reporting periods were chosen as a main focus of the report?The period from 2005-2009 was used for describing the U.S. burden of cancer (rates), and the period from 2000-2009 was used for describing trends in cancer incidence and death rates among the country’s five major racial and ethnic groups. The period from 1975-2009 was chosen to represent the best perspective on long-term trends in cancer death rates among all races combined, while the period from 1992-2009 was chosen to represent the best perspective on long-term incidence trends.

4. What is detailed in the special feature section of this year’s report?In this year’s special feature section, the authors highlight the burden and trends in HPV-associated cancers among men and women ages 15 years and older as well as HPV vaccination coverage levels among adolescent girls ages 13 through 17 years in two years: 2008 and 2010. The report also presents the prevalence of Pap testing (cervical cancer screening) among women ages 21 through 65 in 2010.

Update on Incidence and Mortality Trends for All Cancer Sites Combined and the Most Common Cancers

5. What is happening with cancer incidence trends overall?From 2000 through 2009, incidence rates for all cancers combined declined 0.6 percent per year among men and were stable among women, and increased by 0.6 percent per year among children 14 years and under (see Table 1 of the Report).

Declines in cancer mortality rates are always good news, but the same is not always true for incidence rates. Declines in cancer incidence rates that occur as a result of decreased modifiable risk factors or increased use of those screening tests (colorectal and cervical cancer screening) that allow the detection and removal of precancerous lesions are good news. However, a drop in screening rates can also make it appear that incidence rates are lower while in fact some cancers will not be detected early and may not be discovered until they are at a more advanced stage.

6. What is happening with long-term incidence trends for the most common cancers?From 2000-2009, incidence rates decreased for five of the 17 most common cancers among men (prostate, lung, colon and rectum, stomach, and larynx). In contrast, incidence rates increased among men for six cancers (kidney, pancreas, liver, thyroid, melanoma of the skin, and myeloma) during the same time period (see Table 1 of the Report).

Among women, incidence rates from 2000-2009 decreased for seven of the 18 most common cancers (lung, colon and rectum, bladder, cervix, oral cavity and pharynx, ovary, and stomach), and increased for seven cancers (thyroid, melanoma of the skin, kidney, pancreas, leukemia, liver, and uterus).

Incidence rates were stable for the other most common cancers in men and women from 2000-2009, including female breast cancer and non-Hodgkin lymphoma.

Note that findings are presented for the top 17 cancers among men and 18 cancers among women in order to accommodate the top 15 cancers for all races and ethnicities combined and for each major racial and ethnic group.

7. What is happening with cancer mortality trends overall?Overall cancer death rates continued to decline, a trend that began in the early 1990s. From 2000 through 2009, death rates decreased by 1.8 percent per year among men, by 1.4 percent per year among women, and by 1.8 percent per year among children ages 0-14 and 0-19 years (see Table 2 of the Report). Death rates are the best indicator of progress against cancer.

8. What is happening with death rates for the most common cancers among men and women?For the most recent 10-year period (2000-2009), death rates among men decreased for 10 of the 17 most common cancers (lung, prostate, colon and rectum, leukemia, non-Hodgkin lymphoma, kidney, stomach, myeloma, oral cavity and pharynx, and larynx) and increased for four others (cancer of the pancreas, liver, soft tissue including heart, and melanoma of the skin) (see Table 2 of the Report).

During the same period, death rates among women decreased for 15 of the 18 most common cancers (lung, breast, colon and rectum, ovary, leukemia, non-Hodgkin lymphoma, brain and other central nervous system, myeloma, kidney, stomach, cervix, bladder, esophagus, oral cavity and pharynx, and gallbladder) and increased for cancers of the pancreas, liver, and uterus.

9. If cancer death rates continue to fall, does that mean the number of people dying from cancer will also continue to fall?Not necessarily. The data described in the report are rates (number of deaths per 100,000 persons in the United States) and are adjusted for age so they can be compared across groups that vary by factors such as race, time period, and regions with different age structures. The actual number of people dying from cancer (sometimes called the count) can be influenced by several factors, including the growth in the number of older people in the United States (cancer is primarily a disease of aging) and the increase in size of the population.

Therefore, although the cancer death rate may go down in a given year, the actual number of cancer deaths could go up because the number of older Americans is increasing and the size of the population overall is increasing,

10. What is happening with childhood cancer rates?Cancer incidence rates increased 0.6 percent each year from 1992 through 2009 among children ages 14 years or younger. However, considerable progress has been seen for many types of childhood cancers, resulting in overall declines in death rates for cancer among children since at least 1975. In the most recent 10-year period, cancer death rates among children ages 0 to14 years and 0 to 19 years declined 1.8 percent per year.

11. Why is it important to monitor the burden of and trends in HPV-associated cancers and HPV vaccination coverage levels?Due to recent advances in our understanding of HPV-associated cancers in the U.S., an updated evaluation of the burden and trends in this diverse spectrum of diseases is needed to inform cancer prevention and control programs as well as to inform the public. Notably, HPV-associated cancers have been receiving additional attention from the cancer research community and were the focus of the current President’s Cancer Panel, underscoring the importance of updated knowledge regarding the occurrence of these cancers in the U.S.

Monitoring trends in HPV vaccination coverage levels is useful to ensure the equitable uptake of the vaccine among different population subgroups. It also highlights the important role of vaccination in the prevention of both cervical and non-cervical HPV-associated cancers.

12. What cancers are associated with HPV infection?Virtually all cervical cancers are due to HPV infection, along with 90 percent of anal cancers, more than 60 percent of certain sub-sites of oropharyngeal cancers (including the base of the tongue, tonsils, and other oropharynx), and approximately 40 percent of vagina, vulva, and penile cancers are associated with HPV infection.

13. What is the burden of HPV-associated cancers in the United States?In 2009, a total of 34,788 HPV-associated cancers occurred among men and women (13,466 and 21,342, respectively) in the United States based on cancer registries that cover about 93 percent of the population. These cancers accounted for 3.3 percent of all cancer cases diagnosed in 2009 (See Figure 1of the Report). Cervical cancer alone represents 53.4 percent of the total number of HPV-associated cancers among women and 32.7 percent of all HPV-associated cancers, whereas oropharyngeal cancer accounts for 78.2 percent of HPV-associated cancers among men, 11.6 percent among women, and 37.3 percent among men and women combined. HPV-associated cancers are defined as cancers at specific anatomic sites with specific cellular types in which HPV DNA frequently is found. Not all of these cancers may be HPV-positive because HPV testing was not conducted.

14. What is happening with incidence rates of HPV-associated cancers?From 2000-2009, incidence rates increased for HPV-associated oropharyngeal cancer among white men and women, for anal cancer among white and black men and women, and for cancer of the vulva among white and black women (see Figure 3 of the Report). In contrast, cervical cancer incidence rates decreased for women in all racial and ethnic groups except American Indian/Alaska Native women. Trends for other HPV-associated cancers are provided in Figure 3 in the Report.

15. Which cancers does the HPV vaccine prevent and who should receive it?Two vaccines (known as bivalent and quadrivalent) are available to protect against HPV types 16 and 18, which account for most HPV-associated cancers. Both vaccines are approved for the prevention of cervical cancers caused by HPV types 16 and 18; the quadrivalent vaccine has also been approved for prevention of vaginal, vulvar, and anal cancers. No data are available on their ability to prevent HPV-associated lesions of the oropharynx. The quadrivalent vaccine also protects against HPV types 6 and 11, which cause most genital warts.

The CDC Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination of girls ages 11 or 12 with three doses of either the bivalent or quadrivalent HPV vaccine and routine vaccination of boys ages 11 or 12 with three doses of quadrivalent vaccine. Vaccination is also recommended for females ages 13 through 26 and males ages 13 through 21 who were not vaccinated previously. Males ages 22 through 26 may also receive the vaccine. For men who have sex with men and for immunocompromised males, ACIP recommends routine vaccination with quadrivalent HPV vaccine as for all males, and vaccination through age 26 years for those who were not vaccinated previously.

16. What is happening with HPV vaccination coverage levels?In 2010, less than half (48.7 percent) of adolescent girls ages 13 through 17 nationwide had received one or more doses of HPV vaccine, and fewer than one in three (32.0 percent) had received three doses (see Table 6 and Figure 4 of the Report). State-level HPV vaccination coverage levels varied widely in 2010. For example, 28.8 percent of adolescent girls in Idaho had received at least one dose compared to 73.0 percent in Rhode Island.

Virtually all socio-demographic groups showed increases in HPV vaccination between 2008 and 2010, although not all the increases were statistically significant (see supplemental Table 2 of the Report). Among girls who initiated the series, and had enough time to complete it before the interview date, three-dose series completion was lower among Hispanics versus non-Hispanic whites and among those living below the poverty level versus those living above the poverty level. Three-dose series completion rates were higher among privately insured girls versus uninsured girls or those with public insurance in 2010.

National HPV vaccination coverage estimates for 2011 were not available for this analysis, but they show that between 2010 and 2011, coverage with at least one dose of the HPV vaccine increased from 48.7 percent to 53 percent; three-dose coverage increased from 32.0 percent to 34.8 percent; and three-dose series completion rates increased from 69.6 percent to 70.7 percent.

17. What is happening with Pap testing among women ages 21-65?Nationally, 86.7 percent of women received a Pap test during the previous three years per a survey in 2010. The prevalence of Pap testing varied by state, ranging from 80 percent in Arkansas, Oregon, and Utah to 93 percent in Massachusetts, where cervical cancer rates are low (see Table 6 of the Report). State-specific Pap test prevalence was generally lower among women without insurance or a usual source of medical care.

How to Read This Report

18. How are cancer incidence and death rates presented?Cancer incidence rates and death rates are typically measured as the number of cases or deaths per 100,000 people per year and are age-adjusted to the 2000 U.S. standard population. When a cancer affects only one sex—for example, prostate cancer—then the number is per 100,000 persons of that sex. The numbers are age-adjusted, which allows for comparison of rates from different populations with varying age composition over time and in different regions.

19. What is annual percent change or APC?The annual percent change (APC) is the average rate of change in a cancer rate per year in a given time frame (i.e., how fast or slowly a cancer rate has increased or decreased each year over a period of years). The APC was calculated for both incidence and death rates. The number is given as a percent, such as: an approximate 1 percent per year decrease. The APC is calculated using joinpoint regression (see below for an explanation of joinpoints).

A negative APC describes a decreasing trend, and a positive APC describes an increasing trend. In this report, all trends mentioned in the text are statistically significant unless noted otherwise. For non-statistically significant trends, terms such as “stable,” “non-significant increase,” and “non-significant decrease” were used.

20. What is average annual percent change or AAPC?The report also uses the average annual percent change (AAPC) as an addendum to the underlying joinpoint (see below for an explanation of joinpoints) annual percent change (APC) trends as a summary measure to compare fixed interval trends among racial and ethnic groups.

The AAPC quantifies the average trend over a fixed period of multiple years.

Similar to the APC, a negative AAPC describes a decreasing trend, and a positive AAPC describes an increasing trend. In this report, all trends are statistically significant unless noted otherwise. For non-statistically significant trends, terms such as “stable,” “non-significant increase,” and “non-significant decrease” were used.

Long-term trends can obscure shorter term changes. Differences in the 5-year and 10-year AAPCs typically identify types of cancer where the 10-year average trend may mask important recent changes. For example, in this report the trend for lung cancer deaths shows a more rapid decline when looking at the 5-year AAPC than the 10-year AAPC.

21. What is joinpoint regression analysis, and how does it account for the different time periods used for trends analysis in this report?Joinpoint regression analysis is a statistical method that describes changing trends over successive segments of time and the amount of increase or decrease within each segment. This analysis involves fitting a series of joined straight lines to the age-adjusted rates and choosing the best-fitting point or points, called joinpoints, where the rate of increase or decrease changes significantly. Thus, each joinpoint denotes a statistically significant change in trend. The resulting line segment between joinpoints can be described by an annual percent change that is based on the slope of the line segment. Joinpoint analyses were performed for incidence and mortality trends.

22. Why are absolute changes versus relative changes presented to assess changes in vaccination coverage levels?Absolute percentage increase is used because it most closely reflects the improvement in the number of adolescents protected against HPV infection. Relative percentage increase, in contrast, cannot be directly translated into an increase in the number of individuals protected because the true increase in the number of protected individuals cannot be determined.

For example, in a hypothetical population of 10,000 individuals with baseline vaccination coverage of 50 percent, an absolute increase of 10 percent would correspond to 60 percent coverage and 1,000 additional people protected. On the other hand, a relative increase of 10 percent would correspond to 55 percent coverage (10 percent of 50 percent = 5 percent) and 500 additional people protected.

23. Why were rates adjusted for delays in reporting incidence data to SEER?The report presents analyses of long-term trends in cancer incidence rates with and without adjustment for reporting delays and more complete information. Adjusting for these delays and accumulating more complete and accurate information provides the basis for a potentially more definitive assessment of incidence rates and trends, particularly in the most recent years for which data are available. Cancer registries routinely take two to three years to compile their current cancer statistics. An additional one to two years may be required to have more complete incidence data on certain cancers, such as melanomas and leukemias when they are diagnosed in outpatient settings. Cancer registries continue to update incidence rates to include these cases. Consequently, the data initially reported for certain cancer incidence rates may be an underestimate. Long-term reporting patterns in NCI’s SEER registries have been analyzed, and it is now possible to adjust incidence rates for all cancers combined and for site-specific cancers with a correction for expected reporting delays and more complete information. However, SEER registries do not cover the entire population, thus combined data from SEER and CDC’s National Program of Cancer Registries (which is not delay adjusted) is important for assessing the incidence of cancer in the United States. Methodologic research is in progress to adjust for reporting delays of pooled data from SEER and the National Program of Cancer Registries.

Other Information

24. What other data issues need to be considered?This report uses 2001-2009 postcensal population estimates (which quantify changes since the previous census) from the U.S. Census Bureau to calculate incidence and death rates. Differences between the true population counts and postcensal population estimates may have increased as time has passed from the 2000 Census. These differences may result in incidence and death rates being either underestimated or overestimated.